The delivery of water-insoluble drugs to targets within the human body is a challenge that presently places strict limitations on what drugs can be applied clinically. The need for methods which overcome this is of high priority in the development of new therapeutics for treatment of human disease.
The development of antibiotics for control of pathogenic bacteria has been of pressing need in this era of drugresistant infections. N-Methylthiolated b-lactams have been identified as a new family of antibacterial agents active against Staphylococcus bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). (See Turos, E.; Konaklieva, M. I.; Ren, R. X. F.; Shi, H.; Gonzalez, J.; Dickey, S.; Lim, D. Tetrahedron 2000, 56, 5571; Bart Heldreth, Timothy E. Long, Seyoung Jang, Suresh K. R. Guntireddygari, Edward Turos, Sonja Dickey, Daniel V. Lim, “N-Thiolated b-Lactam Antibacterials: Effects of the N-Organothio Substituent on anti-MRSA Activity,” Bioorganic and Medicinal Chemistry 14, 3775-3784 (2006); and Edward Turos, Jeung-Yeop Shim, Yang Wang, Kerriann Greenhalgh, G. Suresh Kumar Reddy, Sonja Dickey, Daniel V. Lim, “Antibiotic-Conjugated Polyacrylate Nanoparticles: New Opportunities for Development of Anti-MRSA Agents,” Bioorganic and Medicinal Chemistry Letters 16, in press (2006); which are incorporated herein by reference).
The compounds have also displayed promising anticancer properties. These lactams exert their growth inhibitory effects on bacteria through a mode of action that is distinctively different to that of other b-lactam antibiotics, and possess structure-activity patterns unlike those already mapped for other b-lactam antibacterials such as the penicillins. One of the major limitations in the potential application of these N-thiolated b-lactam compounds, however, is their exceedingly low water solubility.
Drug delivery vehicles such as liposomes and gold nanoparticles have been developed to improve bioavailability, efficacy, and specificity of pharmaceutical compounds, particularly for anticancer agents, but nanoparticles have received surprisingly little attention in the antibiotic and infectious disease area. Some of the few notable examples have included antibiotic-encapsulated polymeric nanoparticles and liposomes, biodegradable nanospheres and surface-coated gold and silver nanoparticles.